TM9SF4 is an F-actin disassembly factor that promotes tumor progression and metastasis

Zhaoyue Meng, Zhichao Li, Mingxu Xie, Hongyan Yu, Liwen Jiang () and Xiaoqiang Yao ()
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Zhaoyue Meng: The Chinese University of Hong Kong
Zhichao Li: The Chinese University of Hong Kong
Mingxu Xie: The Chinese University of Hong Kong
Hongyan Yu: The Chinese University of Hong Kong
Liwen Jiang: The Chinese University of Hong Kong
Xiaoqiang Yao: The Chinese University of Hong Kong

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract F-actin dynamics is crucial for many fundamental properties of cancer cells, from cell-substrate adhesion to migration, invasion and metastasis. However, the regulatory mechanisms of actin dynamics are still incompletely understood. In this study, we demonstrate the function of a protein named TM9SF4 in regulating actin dynamics and controlling cancer cell motility and metastasis. We show that an N-terminal fragment (NTF) cleaved from TM9SF4 can directly bind to F-actin to induce actin oxidation at Cys374, consequently enhancing cofilin-mediated F-actin disassembly. Knockdown of TM9SF4 reduces cell migration and invasion in ovarian cancer cells A2780, SKOV3 and several high grade serous ovarian cancer lines (HGSOCs). In vivo, knockdown of TM9SF4 completely abolishes the tumor growth and metastasis in athymic nude mice. These data provide mechanistic insights into TM9SF4-mediated regulation of actin dynamics in ovarian cancer cells.

Date: 2022
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DOI: 10.1038/s41467-022-33276-y

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